Role of FOXM1 in vascular smooth muscle cell survival and neointima formation following vascular injury.
Apoptosis
Biological sciences
Cell biology
FOXM1
Intimal hyperplasia
Molecular biology
Pathology
Pathophysiology
Proliferation
Smooth muscle cell
Journal
Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
07
08
2019
revised:
15
03
2020
accepted:
15
05
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
25
6
2020
Statut:
epublish
Résumé
Accelerated smooth muscle cell (SMC) proliferation is the primary cause of intimal hyperplasia (IH) following vascular interventions. Forkhead Box M1 (FOXM1) is considered a proliferation-associated transcription factor. However, the presence and role of FOXM1 in IH following vascular injury have not been determined. We examined the expression of FOXM1 in balloon-injured rat carotid arteries and investigated the effect of FOXM1 inhibition in SMCs and on the development of IH. FOXM1 was detected by immunofluorescent staining in balloon-injured rat carotid arteries where we observed an upregulation at day 7, 14, and 28 compared to uninjured controls. Immunofluorescence staining revealed FOXM1 coincided with proliferating cell nuclear antigen (PCNA). FOXM1 was also detectable in human carotid plaque samples. Western blot showed an upregulation of FOXM1 protein in serum-stimulated SMCs. Inhibition of FOXM1 using siRNA or chemical inhibition led to the induction of apoptosis as measured by flow cytometry and western blot for cleaved caspase 3. Perturbations in survival signaling were measured by western blot following FOXM1 inhibition, which showed a decrease in phosphorylated AKT and β-catenin. The chemical inhibitor thiostrepton was delivered by intraperitoneal injection in rats that underwent balloon injury and led to reduced intimal thickening compared to DMSO controls. FOXM1 is an important molecular mediator of IH that contributes to the proliferation and survival of SMCs following vascular injury.
Sections du résumé
BACKGROUND
BACKGROUND
Accelerated smooth muscle cell (SMC) proliferation is the primary cause of intimal hyperplasia (IH) following vascular interventions. Forkhead Box M1 (FOXM1) is considered a proliferation-associated transcription factor. However, the presence and role of FOXM1 in IH following vascular injury have not been determined.
OBJECTIVE
OBJECTIVE
We examined the expression of FOXM1 in balloon-injured rat carotid arteries and investigated the effect of FOXM1 inhibition in SMCs and on the development of IH.
METHODS AND RESULTS
RESULTS
FOXM1 was detected by immunofluorescent staining in balloon-injured rat carotid arteries where we observed an upregulation at day 7, 14, and 28 compared to uninjured controls. Immunofluorescence staining revealed FOXM1 coincided with proliferating cell nuclear antigen (PCNA). FOXM1 was also detectable in human carotid plaque samples. Western blot showed an upregulation of FOXM1 protein in serum-stimulated SMCs. Inhibition of FOXM1 using siRNA or chemical inhibition led to the induction of apoptosis as measured by flow cytometry and western blot for cleaved caspase 3. Perturbations in survival signaling were measured by western blot following FOXM1 inhibition, which showed a decrease in phosphorylated AKT and β-catenin. The chemical inhibitor thiostrepton was delivered by intraperitoneal injection in rats that underwent balloon injury and led to reduced intimal thickening compared to DMSO controls.
CONCLUSIONS
CONCLUSIONS
FOXM1 is an important molecular mediator of IH that contributes to the proliferation and survival of SMCs following vascular injury.
Identifiants
pubmed: 32577545
doi: 10.1016/j.heliyon.2020.e04028
pii: S2405-8440(20)30872-0
pii: e04028
pmc: PMC7303564
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e04028Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL122562
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL110853
Pays : United States
Informations de copyright
© 2020 The Author(s).
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